Does epilepsy contribute to the clinical phenotype of C9orf72 mutation in fronto-temporal dementia?

C9orf72 mutation is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Recently, several reports of patients with FTD who carried the C9orf72 mutation and also manifested epilepsy have been published, since seizures occur in FTD at a higher rate than in the general population, the possible association between epilepsy and C9orf72 mutation remains to be clarified. In the attempt to understand whether epilepsy contributes to the phenotype of the C9orf72 mutation, we compared epilepsy occurrence in patients with FTD who carried the C9orf72 mutation and those who did not. In our sample of 84 patients with FTD, 7.1% of cases reported epilepsy, with no significant differences between subsamples of patients with FTD stratified according to the presence of the C9orf72 mutation or to family history of FTD/parkinsonism/motor neuron disease. Our findings did not support to the possibility that epilepsy represents a characteristic feature of the C9orf72 mutation, as suggested by recent case reports published in the English literature.

Incidence of amyotrophic lateral sclerosis in Sardinia, Italy: age-sex interaction and spatial-temporal variability.

Objective: This study assessed amyotrophic lateral sclerosis (ALS) incidence in Sardinia, Italy, and the combined contribution of age and gender to disease risk. We also checked disease incidence for spatial-temporal variability. Methods: ALS patients from all neurological centers of the study area who had onset during 2010-2019 and fulfilled El Escorial revised diagnostic criteria were included. Incidence was calculated for the overall study area and each province separately. Additive interaction between age and sex on ALS incidence was assessed. Results: The average crude annual incidence rate was 3.6/100,000 person-years (95% CI, 3.2-4.1), 3.1/100,000 person-years (95% CI, 2.7-3.5) when age-adjusted. Incidence was greater among people aged ≥65 years and men, with the two variables undergoing significant additive interaction. Incidence increased yearly over the study period, with annual incidence correlating with the increasing yearly frequency of people aged ≥65 years, but not with the proportion of incident cases carrying genetic mutations. Stratifying by province, the rates from Oristano and South Sardinia were higher than the rate from Cagliari. ALS patients from areas at different risk were comparable for frequency of clinical/genetic features. Conclusion: ALS incidence in Sardinia was in the upper part of the European range of variability. We also provided new information about age and sex as risk factors for ALS, showing male sex as a modifier of the effect of aging on ALS incidence. Spatial-temporal variations in ALS incidence correlated to changes in the proportion of the aging population rather than to the distribution of genetic factors.

Sudoscan in the evaluation and follow-up of patients and carriers with TTR mutations: experience from an Italian Centre.

OBJECTIVE: To evaluate the utility of Sudoscan as possible marker of disease progression and disease onset in a cohort of hereditary ATTR amyloidosis (hATTR amyloidosis) polyneuropathy patients and carriers. PATIENTS AND METHODS: We regularly performed different clinical scales, nerve conductions studies (NCS), and Sudoscan on a cohort of hATTR amyloidosis patients and carriers from a single centre of central Italy, a non-endemic area, in the last 2 years. RESULTS: About 18 hATTR amyloidosis patients and 8 asymptomatic carriers were enrolled. All patients had a neuropathy affecting large fibres, small fibres or both. Two subjects developed symptoms and neurophysiological alterations during follow-up. Sudoscan data from hand and feet inversely correlated with neuropathy severity and with disease duration. Moreover, global disease status, expressed by Kumamoto scale also inversely correlated with Sudoscan values. CONCLUSIONS: We confirmed that Sudoscan is a reliable marker of disease progression in late-onset hATTR amyloidosis patients and we suggest its possible utility in early detection of disease in this population.